EP0442204A2 — Pyrimidopyrimidine derivatives, process and intermediates for their preparation and pharmaceutical compositions containing them

USPTO Abstract

Compounds of the formula (1): and pharmaceutically acceptable salts are described wherein R¹ is C₁₋₆alkyl, C₂₋₆alkenyl, C₃₋₅cycloalkyl C₁₋₆alkyl, or C₁₋₆alkyl substituted by 1 to 6 fluoro groups; R² is C₁₋₆alkylthio, C₁₋₆alkylsulphonyl, C₁₋₆alkoxy, hydroxy, hydrogen, hydrazino, C₁₋₆alkyl, phenyl, ―NHCOR³ wherein R³ is hydrogen or C₁₋₆alkyl, or ―NR⁴R⁵, wherein R⁴ and R⁵ together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino ring, or R⁴ and R⁵ are independently hydrogen, C₃₋₅cycloalkyl or C₁₋₆alkyl which is optionally substituted by ―CF₃, phenyl, ―S(O) n C₁₋₆alkyl wherein n is 0, 1 or 2, ―OR⁶, ―CO₂R⁷ or ―NR⁸R⁹ wherein R⁶ to R⁹ are independently hydrogen or C₁₋₆alkyl, provided that the carbon atom adjacent to the nitrogen atom is not substituted by said ―S(O) n C₁₋₆alkyl, ―OR⁶ or ―NR⁸R⁹ groups; R is halo, C₁₋₄alkyl, C₁₋₄ alkoxy, cyano, ―CONR¹⁰R¹¹, CO₂R¹², C₁₋₄alkylS(O) n , ―NO₂, ―NH₂, ―NHCOR¹³ or SO₂NR¹⁴R¹⁵ wherein n is 0, 1 or 2 and R¹⁰ to R¹⁵ are independently hydrogen or C₁₋₄alkyl; and is a ring of sub-formula (a) or (b) : These compounds have bronchodilatator, anti-allergic, and vasodilator activities. Pharmaceutical compositions are described as are methods of use. Processes for the preparation of compounds of the formula (1) are described.